The possibility that the neuropeptide cholecystokinin (CCK) was co-localized with dopamine (DA) was examined in rats with unilateral 6-hydroxydopamine (6OHDA) or mechanical hemitransection of the mesolimbic DA system. The effects of the lesions on CCK content and tyrosine hydroxylase (TH) activity were evaluated in the olfactory tubercle (OT) and nucleus accumbens (NA) (representative of the meso-limbic system) and the caudate-putamen (CP) (representative of the nigrostriatal system). After hemisection the maximal loss of CCK was 50-60% in OT and NA; no change was observed in CP despite decreases of 85-97% in TH activity. Similar effects upon CCK and TH were observed with 6OHDA lesion placed in the ventral tegmental area; whereas 6OHDA placed laterally in the substantia nigra had little impact on CCK content of either OT, NA or CP. These results suggest that: 1) a substantial proportion of the CCK content of OT and NA may be derived from DA neurons, 2) DA-CCK co-localization appears to be mainly a feature of the mesolimbic system rather than the nigrostriatal system and 3) the remaining CCK in OT and NA and the majority of CCK in CP derived from another, most likely cortical source.